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Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.


ABSTRACT: Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. Here we review what computer, in vitro, in vivo, and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP, and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D), and amyotrophic lateral sclerosis (ALS) research, respectively, for many years.

SUBMITTER: Nguyen PH 

PROVIDER: S-EPMC8836097 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.

Nguyen Phuong H PH   Ramamoorthy Ayyalusamy A   Sahoo Bikash R BR   Zheng Jie J   Faller Peter P   Straub John E JE   Dominguez Laura L   Shea Joan-Emma JE   Dokholyan Nikolay V NV   De Simone Alfonso A   Ma Buyong B   Nussinov Ruth R   Najafi Saeed S   Ngo Son Tung ST   Loquet Antoine A   Chiricotto Mara M   Ganguly Pritam P   McCarty James J   Li Mai Suan MS   Hall Carol C   Wang Yiming Y   Miller Yifat Y   Melchionna Simone S   Habenstein Birgit B   Timr Stepan S   Chen Jiaxing J   Hnath Brianna B   Strodel Birgit B   Kayed Rakez R   Lesné Sylvain S   Wei Guanghong G   Sterpone Fabio F   Doig Andrew J AJ   Derreumaux Philippe P  

Chemical reviews 20210205 4


Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. H  ...[more]

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